Title:Arylurea Derivatives: A Class of Potential Cancer Targeting Agents
Volume: 17
Issue: 28
Author(s): Jia-Nian Chen*, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou*, Shi-Ming Pu and Wan-Hua Lin
Affiliation:
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi,China
- Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi,China
Keywords:
Arylurea, Anti-cancer, Signaling pathway inhibitor, Tumor angiogenesis inhibitor, Tumor migration and invasion
inhibitor, Structure-activity relationship.
Abstract: Arylurea derivatives, an important class of small molecules, have received considerable attention
in recent years due to their wide range of biological applications. Various molecular targeted agents
with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development
of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer
activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided
into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor
angiogenesis inhibitors, their targets include Vascular Endothelial Growth Factor Receptors (VEGFRs),
Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs),
Epidermal Growth Factor Receptors (EGFRs), Insulin-Like Growth Factor 1 Receptor (IGF-1R), Fmslike
Tyrosine Kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling
pathway inhibitors; (4) cell cycle inhibitors, their targets include Checkpoint Kinases (Chks), Cyclin-
Dependent Kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5)
tumor differentiation, migration, and invasion inhibitors, their targets include Matrix Metalloproteinases
(MMPs), LIM kinase (Limk), Nicotinamide Phosphoribosyltransferase (Nampt), and Histone Deacetylase
(HDAC); (6) arylureas from the rational modification of natural products. This review focuses on
the Structure-Activity Relationships (SARs) of these arylureas. The structural evolution and current
status of some typical anti-cancer agents used in clinic and/or in clinical trials are emphasized.
